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Biomedical subjects

J R Wilson

Publications and source records attributed to J R Wilson.

At least 19 recordsLinked to original sources

The utility of exercise testing after cardiac transplantation in older patients.

BACKGROUND: The criteria for cardiac transplantation recipient selection, including the appropriate recipient upper age limit, continue to expand with an increasing number of recipients greater than 60 years of age. While others have reported their transplant experience in older recipients in terms of quality of life assessment, we have examined the role of exercise cardiopulmonary testing post-transplantation in older cardiac transplant recipients. METHODS: We reviewed inpatient and outpatient charts of 28 patients 60 years of age or older who underwent orthotopic heart transplantation at Vanderbilt University Medical Center. RESULTS: In this population, perioperative mortality of 7.1% and Kaplan-Meier survival at 1 and 5 years of 89 and 77%, respectively, were similar to the institutional 1-year (89%) and 5-year (75%) survival among younger adult transplant recipients. Exercise cardiopulmonary testing results were available in 22/25 patients surviving greater than 1 year. Both peak oxygen consumption and percentage of maximum VO2 were significantly greater among patients reporting NYHA Class 1 or 2 functional status, in comparison with those NYHA Class 3 or greater. CONCLUSION: Following cardiac transplantation, survival of patients greater than 60 years of age is equivalent to that of younger patients at our institution. Exercise testing provides an objective measure of performance and correlates with subjective status following heart transplantation. Most patients demonstrate good functional status, with minimal symptoms and good exercise capacity. These results, although retrospective, suggest that cardiac transplantation remains a reasonable therapeutic option for patients greater than 60 years of age with end-stage cardiomyopathy.

Aged

Impact of a nurse practitioner on the cost of managing inpatients with heart failure.

We examined the impact on hospital costs of having a nurse practitioner manage uncomplicated patients hospitalized for decompensated heart failure. This strategy was associated with a significant decrease in total hospital costs ($6,659+/-5,843 vs $5,211+/-4,137 [p < 0.03]), a trend toward decreased length of stay (4.0+/-3.0 vs 3.4+/-2.4 days [p = 0.13]), and no significant change in the 30-day readmission rate (13% of patients vs 16% of patients [p = NS]).

Adult

Nutrient stimulation results in a rapid Ca2+-dependent threonine phosphorylation of myosin heavy chain in rat pancreatic islets and RINm5F cells.

Activation of protein kinases plays an important role in the Ca2+-dependent stimulation of insulin secretion by nutrients. The aim of the present study was to identify kinase substrates with the potential to regulate secretion because these have been poorly defined. Nutrient stimulation of the rat insulinoma RINm5F cell line and rat pancreatic islets resulted in an increase in the threonine phosphorylation of a 200-kDa protein. This was secondary to the gating of voltage-dependent Ca2+ channels because it was reproduced by depolarizing KCl concentrations and blocked by the Ca2+ channel antagonist, verapamil. The peak rises in [Ca2+]i preceded or were coincident with the maximal threonine phosphorylation in response to both glyceraldehyde and KCl. In digitonin-permeabilized RINm5F cells a rise in Ca2+ from 0.1 to 0.15 microM was sufficient to increase phosphorylation. Protein kinase C, protein kinase A, and Ca2+/calmodulin-dependent kinase II did not appear to be responsible for the phosphorylation, yet the Ca2+ dependence of the response suggests possible involvement of other members of the Ca2+/calmodulin-dependent kinase family. The 200-kDa protein was identified as myosin heavy chain by immunoprecipitation with a polyclonal nonmuscle myosin antibody. Phosphopeptide mapping indicated that the site of phosphorylation on myosin heavy chain was the same for both KCl- and glyceraldehyde-stimulated cells. Phosphoamino acid analysis confirmed a low basal phosphothreonine content of myosin heavy chain, which increased 6-fold in response to KCl. A lesser (2-fold) increase in serine phosphorylation was also detected using this technique. Although myosin IIA and IIB were shown to be present in RINm5F cells and rat islets, myosin IIA was the predominant threonine-phosphorylated species, suggesting that the two myosin species might be independently regulated. Our results identify myosin heavy chain as a novel kinase substrate in pancreatic beta-cells and suggest that it might play an important role in the regulation of insulin secretion.

Amino Acids

Frequency of low-risk hospital admissions for heart failure.

Heart failure is one of the most common reasons for admission to acute care hospitals. A proportion of these admissions are probably low risk and could be managed in subacute care facilities, resulting in substantial cost savings. To investigate the proportion of low-risk hospital admissions for heart failure, all admissions for heart failure to Vanderbilt University Medical Center between July 1993 and June 1995 were identified (n = 743). One hundred twenty of these admissions were randomly selected, reviewed, and classified into a high-risk versus low-risk group on admission based on the severity of heart failure and the presence of life-threatening complications. Of the 120 admissions, 57 (48%) were classified as high risk based on the presence of moderate to severe heart failure for the first time or recurrent heart failure with a major complicating factor. Sixteen admissions (28%) were associated with adverse outcomes, including myocardial infarction in 5 (9%), intubation in 6 (11%), and death in 4 (7%). Sixty-three admissions (52%) were classified as low risk based on the presence of new-onset mild heart failure or mild to moderate recurrent heart failure with no complicating factors. Most of these admissions were for dyspnea without any life-threatening complication; 57 (91%) had no evidence of interstitial or alveolar pulmonary edema, and arterial oxygen saturation averaged 95 +/- 3%. Only 3 of these low risk admissions (5%) were associated with an adverse cardiovascular event. None of the patients died. These data suggest that over half of the patients admitted for heart failure to an acute care facility are low risk and probably could be managed in a subacute care setting, resulting in large cost savings.

Aged

Conduction velocity versus amplitude analysis: evidence for demyelination in diabetic neuropathy.

Motor conduction velocities (CVs) were correlated with distal compound muscle action potential (CMAP) amplitudes for tibial, peroneal, and median nerves in patients with biopsy-proven chronic inflammatory demyelinating polyneuropathy (CIDP), diabetic neuropathy, and amyotrophic lateral sclerosis. Only in the diabetic patients did CV significantly correlate with CMAP amplitude. The data show that diabetic neuropathy produces conduction velocity slowing that cannot be explained by axon loss alone, and that differentiation between diabetic neuropathy and CIDP in an individual nerve is difficult.

Action Potentials

Safety pictograms: are they getting the message across?

This study set out to investigate the role of pictograms in conveying consumer safety information. The experimental work was carried out in two parts. The first part investigated UK comprehension levels of 13 product related pictograms. A new method of judging levels of comprehension of the pictograms was developed. In general the pictograms surveyed were found to be poorly understood, particularly those which were abstract in nature. The second part of the research investigated the effect of different warning styles on noticeability and intended compliance. This was tested using the new European Standard pictogram developed to convey the small parts warning on toys. The effect on parents' intended purchase decisions of different pictograms and or text messages was investigated. Results indicated that parents' decisions on toy suitability were influenced by the perceived hazardousness of the product rather than warnings, regardless of their design. The paper discusses the advantages and limitations of pictograms as a method for conveying consumer information and makes recommendations for their effective use.

Consumer Product Safety

Development of directional motion symmetry in the monocular visually evoked potential of infant monkeys.

Motion processing in humans and monkeys exhibit a directional asymmetry during infancy which is not present in adults except following abnormal visual rearing conditions. To characterize the time course for maturation of a symmetric response, we measured the monocular visually evoked potential (MVEP) response to 0.26 c/deg gratings oscillating horizontally at 6 Hz in 13 infant rhesus monkeys between 1 and 52 weeks of age. An asymmetric (F1) and a symmetric (F2) frequency component were extracted from the MVEP using Fourier analysis. At early ages the asymmetric F1 component measured from the two eyes exhibited a 180 deg interocular phase shift, demonstrating that there was a directional bias in opposite directions between the left and right eyes. Although our methods could not determine whether the bias was in the nasal or temporal direction, our results would be consistent with a nasal bias, as has been observed in previous motion studies. Magnitude of the asymmetry was quantified in the form of an asymmetry index, F1/(F1 + F2). Based on developmental changes in the asymmetry index, and phase and amplitudes of F1 and F2, we conclude that the MVEP loses its directional asymmetry at 6 weeks of age. The development of directional motion symmetry observed in monkeys over the first 6 weeks is similar to that observed in humans over the first 5 months.

Aging

Effects of the trichothecene mycotoxin T-2 toxin on neurotransmitters and metabolites in discrete areas of the rat brain.

T-2 toxin has been shown to affect the central nervous system. Only recently have attempts been made to characterize the neurochemical perturbations associated with T-2 intoxication. To examine the effect of T-2 on regional brain biogenic monoamines and selected metabolites, male rats were dosed orally with T-2 toxin in corn oil at 0.1, 1.0 or 2.5 mg/kg body weight. At 2, 6 and 10 hr post-dosing, rats were killed, brains were collected and stored at -80 degrees until analysed. Brain nuclei, including nucleus raphe magnus, paraventricular nucleus, locus coeruleus, substantia nigra, medial forebrain bundle, nucleus accumbens and olfactory tubercle, were analysed. T-2 treatment increased 5-hydroxy-3-indoleacetic acid and serotonin throughout the brain, and produced a transient increase in norepinephrine in the nucleus raphe magnus and a temporary decrease in the substantia nigra. Regional dihydroxyphenylacetic acid concentration was affected, with increased DOPAC observed in the locus coeruleus, medial forebrain bundle and paraventricular nucleus of the hypothalamus, and decreased DOPAC in the olfactory tubercles. No regional changes in epinephrine or dopamine were observed. Few treatment differences were observed, with the 0.1 mg/kg body weight T-2, 2% of the LD50, significantly affecting brain monoamines. It had been suggested that neurological manifestations of T-2 toxin are the result of brain hypoxia; however, the altered brain monoamine profile observed at doses that do not alter heart function, suggests the brain is a primary site of trichothecene action.

3,4-Dihydroxyphenylacetic Acid

Effect of T-2 toxin on blood-brain barrier permeability monoamine oxidase activity and protein synthesis in rats.

Systemic exposure to T-2 toxin disrupts brain biogenic monoamine metabolism. Although the mechanisms underlying these neurochemical perturbations are unclear, we have suggested that they are a reflection of increased blood-brain barrier (BBB) permeability, or altered protein synthesis that affects brain enzyme activities. Accordingly, BBB permeability, in vitro protein synthesis and in vitro monoamine oxidase (MAO) activity were examined in rats after either acute, or 7-day exposure to T-2. Membrane permeability was assessed from the recovery of systemically administered [14C]mannitol and [14C]dextran with [3H]water as the diffusible reference, either 2 hr post-intraperitoneal (i.p.) injections of 0, 0.2 and 1 mg T-2/kg body weight or following a 7-day exposure to diets containing 0 and 10 ppm T-2. Protein synthesis, determined by [14C]leucine incorporation, and MAO activity, determined by H2O2 production, were observed either 2 hr post-ip injection of 0 and 1 mg T-2/kg body weight or following a 7-day exposure to diets containing 0, 2.5 and 10 ppm T-2. Permeability increases were observed in all brain regions examined for mannitol, but not for dextran following T-2 i.p. The effect of dietary T-2 was more modest, affecting mannitol uptake in two brain regions, the cerebellum and pons plus medulla regions. Protein synthesis was significantly decreased by i.p. administration of T-2, while dietary treatment significantly reduced MAO enzyme activity. Collectively, the effect of T-2 toxin on BBB permeability, protein synthesis and MAO enzyme activity may account for the neurochemical imbalance observed in T-2 intoxication.

Animals

Hyperbaric oxygen in the treatment of migraine with aura.

Cephalalgia is one of the most common medical complaints and the search continues for relief. Early treatments for migraine included inhalation of 100% oxygen. It has been theorized that the increased levels of oxygen in the blood act as an alpha-adrenergic agent to alleviate headache pain through vasoconstriction and local metabolic effects. The presence of muscle tenderness during some migraine headaches has also been established. The purpose of this study was to document relief of cephalalgia through use of a visual analog pain scale, algometry, and manual palpation. Female subjects with confirmed migraine were randomly assigned to begin with either the control (100% oxygen, no pressure) or hyperbaric treatment (100% oxygen, pressure). Manual palpation and algometry of 10 sites were done, bilaterally, by a trained specialist. Pain was evaluated with a visual analog scale. Resolution of tenderness and edema following both treatments was observable by manual palpation while algometry showed no differences between the two. Subjective pain was significantly decreased following hyperbaric oxygen treatment but not following the control treatment. Results suggest that hyperbaric oxygen treatment reduces migraine headache pain and that the patient's subjective assessment was the best indicator of relief.

Adult

Median mixed nerve conduction studies in the forearm: evidence against retrograde demyelination in carpal tunnel syndrome.

Motor conduction velocity (CV) measurements often show conduction velocity slowing in the forearm segment of the median nerve in carpal tunnel syndrome (CTS). This is thought to be caused by either retrograde demyelination in the forearm or conduction block of the fastest fibers within the carpal tunnel. Direct measurement of the forearm segment of the median nerve should distinguish these two possibilities. Standard motor conduction studies and mixed nerve action potential (MNAP) recordings were performed on the forearm segment of the median nerve in patients (n = 32 limbs, aged 24 to 76) and controls (n = 15 limbs, aged 33 to 76). CVMot and CVMNAP were compared between patients and controls. The CVMot was significantly slower in patients with CTS than controls (patients 48+/-5 msec, controls 54+/-5 m/s, P = 0.001), but the CVMNAP showed no difference (patients 59+/-5 m/s, controls 60+/-5 m/s, P = 0.5) in the two groups. Additionally, the difference between CVMNAP and CVMot in a given patient was significantly larger in the patient group than in the controls (patients 11+/-4 m/s, controls 6+/-2 m/s, P < 0.0001). These results strongly support the hypothesis that the slowing seen in the forearm is caused by conduction block of the fastest conducting fibers within the carpal tunnel and is not caused by retrograde demyelination.

Adult

Effect of a heart failure program on hospitalization frequency and exercise tolerance.

BACKGROUND: Most patients with heart failure are currently managed by physicians with little specific expertise in heart failure. This management system has been associated with evidence of suboptimal care, such as high rates of hospital readmission and underuse of ACE inhibitors. The current study was undertaken to determine whether hospitalization rates and functional outcomes are improved when patients are managed by physicians with special expertise in heart failure working in a dedicated heart failure program. METHODS AND RESULTS: All patients with heart failure referred to the Vanderbilt Heart Failure and Heart Transplantation Program between July 1994 and June 1995 were identified. Annual hospitalization rates, medications, and peak exercise capacity before and after referral were compared in patients followed for >30 days. A total of 187 patients were referred during the index time period, of whom 134 (72%) were followed for >30 days. During the year before referral, 94% of the patients were hospitalized (210 cardiovascular hospitalizations) versus 44% of the patients during the year after referral (104 hospitalizations) (53% reduction) (P<.01). Hospitalizations for heart failure decreased from 164 to 60 for all patients regardless of follow-up duration and decreased from 97 to 30 (69% reduction) for patients followed at least 1 year after referral. Eighty-eight of the patients were able to exercise at the time of referral. Peak exercise VO2 in this group increased from 12.8+/-4.7 to 15.7+/-4.8 mL x min(-1) x kg(-1) (P<.01) by 6 months after referral. Loop diuretic doses were on averaged doubled during the first 6 months after referral. CONCLUSIONS: These findings suggest that patients with heart failure have fewer hospitalizations for heart failure and are significantly more functional when managed by heart failure specialists working in a dedicated heart failure program rather than by physicians with limited expertise in heart failure.

Adult

Normalization of acquired QT prolongation in humans by intravenous potassium.

BACKGROUND: QT interval prolongation and dispersion have been implicated in serious arrhythmias in congestive heart failure (CHF) and the congenital and drug-induced long-QT syndromes (LQTS). In a subset of the congenital LQTS, infusion of potassium can correct QT abnormalities, consistent with in vitro increases in outward currents such as I(Kr) or I(Kl) when extracellular potassium concentration ([K+]o) is increased. Furthermore, increasing [K+]o decreases the potency of I(Kr)-blocking drugs in vitro. The purpose of this study was to test the hypothesis that increasing [K+]o corrects QT abnormalities in CHF and in subjects treated with quinidine. METHODS AND RESULTS: KCl (maximum, 40 mEq) was infused into (1) 12 healthy subjects treated with quinidine sulfate (5 doses of 300 mg/5 h) or placebo and (2) 8 CHF patients and age-matched normal control subjects. Mean [K+] increased from 4 to 4.2 mEq/L to 4.7 to 5.2 mEq/L. Potassium infusion significantly reversed QTUc prolongation, especially in the precordial leads (quinidine, 590+/-79 to 479+/-35 [+/-SD] ms(1/2), P<.001; CHF, 521+/-110 to 431+/-47 ms(1/2), P<.05). There was no effect in either control group. Similarly, potassium decreased QTUc dispersion (quinidine, 210+/-62 to 130+/-75 ms(1/2), P<.01; CHF, 132+/-68 to 84+/-35 ms(1/2), P=.07) and was without effect in the control subjects. QT morphological abnormalities, including U waves and bifid T waves, were reversed by potassium. CONCLUSIONS: Potentially arrhythmogenic QT abnormalities during quinidine treatment and in CHF can be nearly normalized by modest elevation of serum potassium.

Adult

Effect of sympathoinhibition on exercise performance in patients with heart failure.

BACKGROUND: In patients with heart failure, excessive sympathetic activation during exercise could interfere with exercise performance by impairing arteriolar dilation in working muscle and by adversely altering skeletal muscle metabolic behavior. To test this hypothesis, we examined the effect of sympathoinhibition with clonidine, a central sympatholytic agent, on skeletal muscle blood flow and metabolism in patients with heart failure. METHODS AND RESULTS: Swan-Ganz and femoral venous catheters were inserted in 20 patients with chronic heart failure and exercise intolerance (peak exercise VO2 = 9.3 +/- 1.4 [SEM] mL.min-1.kg-1). Central hemodynamic measurements, leg blood flow determined by thermodilution, and systemic and leg metabolic parameters were measured during maximal treadmill exercise before and 2 hours after clonidine 2 micrograms/kg IV (n = 15) or 0.9% normal saline (n = 5). During-control exercise before the administration of clonidine, leg blood flow increased from 0.3 +/- 0.1 to 1.8 +/- 0.2 L/min and plasma norepinephrine increased from 485 +/- 61 to 2155 +/- 186 pg/mL (both P < .01). Treatment with clonidine markedly suppressed norepinephrine levels during exercise (matched peak exercise workload: control, 2137 +/- 187 versus clonidine, 1430 +/- 161 pg/mL), increased leg blood flow (control, 1.8 +/- 0.2 versus clonidine, 2.3 +/- 0.4 L/min), reduced systemic oxygen consumption (control, 1002 +/- 70 versus clonidine, 966 +/- 68 mL/min), reduced pulmonary artery lactate concentration (control, 3.2 +/- 0.3 versus clonidine, 2.6 +/- 0.2 mEq/L), and decreased minute ventilation (control, 39.7 +/- 2.1 versus clonidine, 34.9 +/- 2.4 L/min) (all P < .05). CONCLUSIONS: These findings suggest that sympathetic activation during exercise reduces leg blood flow, increases muscle glycolysis, and decreases muscle efficiency in patients with heart failure.

Cardiomyopathy, Dilated

Hemolytic anemia associated with intravenous immunoglobulin.

Intravenous immunoglobulin (IVIg) is a useful tool in the treatment of a variety of neuromuscular disorders. Though IVIg therapy is generally safe, hemolytic anemia is a potentially serious complication that is often overlooked, and is currently not listed in product inserts. We analyzed 45 patients who received IVIg therapy, including 38 consecutive patients who received IVIg over a 13-month period. On 42 patients, direct antiglobulin testing was performed, searching for antibodies to the patients' own blood type. Of these 42 patients, 12 developed passive sensitization with antibodies to their own blood group antigens after receiving IVIg. Of these 12 patients, 11 patients developed hemolysis severe enough to lower the hemoglobin level by at least 1 g/dL. Of these patients, 3 required blood transfusion, and 1 had IVIg therapy truncated because of the hemolysis. Antibodies to blood group antigens are found in all commercial preparations of IVIg. Though most patients do not have clinically significant hemolysis, clinicians should be aware of this potentially serious complication. Careful monitoring of hemoglobin levels during IVIg therapy is recommended.

Anemia, Hemolytic

Irrelevant speech and irrelevant tones: the relative importance of speech to the irrelevant speech effect.

Irrelevant auditory stimuli disrupt immediate serial recall. In the equipotentiality hypothesis, D. M. Jones and W. J. Macken (1993) made the controversial prediction that speech and tones have an equivalent disruptive effect. In the present study, 5 experiments tested their hypothesis. Experiments 1-4 showed that meaningful speech disrupts recall more than do tones. Experiments 3 and 4 provided some evidence that meaningful speech disrupts recall more than does meaningless speech, and Experiment 4 showed that even meaningless speech disrupts recall more than do tones. Using slightly different experimental procedures, Experiment 5 showed that letters disrupt recall more than do tones. Implications of these results for a number of theories of primary memory and the irrelevant speech effect are discussed.

Adult